To enhance the immune-activating capacity of an antigen, an adjuvant is used together with the antigen. Although complete Freund's adjuvant (CFA) is known to have an excellent effect as an adjuvant, CFA is composed of killed bacteria and an oil emulsion and, hence, has strong side effects such as strong inflammatory reaction and formation of ulcerative swelling (granuloma) at the administration site. Therefore, use of CFA for humans is not permitted in view of safety. Accordingly, adjuvants whose administration to humans is permitted are limited.
Examples of adjuvants whose administration to humans is permitted include aluminum hydroxide adjuvants, but their immune-activating capacities are not necessarily sufficient and, hence, they need to be repeatedly administered to achieve acquisition of immunity. Therefore, development of an immunogenic composition using an efficient and strong adjuvant, which composition can be used for humans, has been demanded.
To develop a novel adjuvant aiming to attain a high immune-activating capacity, a method wherein an antigen is encapsulated in a microparticle has been attempted. It has been reported that administration of a microparticulated antigen enhances immunological reactions such as antibody production compared to administration of an antigen alone, but the effect of its administration is not necessarily high, and only an effect at almost the same level as in the above-mentioned aluminum hydroxide adjuvant has been reported. This is considered to be due to the difficulty in efficiently encapsulating hydrophilic antigen molecules such as proteins in microparticles studied so far such as microparticles composed of hydrophobic polylactic acid-polyglycolic acid copolymers while maintaining the structures of the antigen molecules (Advanced Drug Delivery Reviews, 2005, Vol. 57, pp. 391-410).
In recent years, a novel microparticle technology has been reported (WO 2006/095668 and JP 2008-088158 A), which technology uses an amphiphilic polymer and enables highly efficient encapsulation of a high molecular weight protein. Although this novel microparticle has been studied for its sustained-release performance for drugs, its adjuvant function in cases of encapsulation of an antigen therein has not been studied at all. Further, in terms of the mechanism by which a microparticle containing an antigen functions as an adjuvant, it is thought that the function for sustained release of the antigen molecule as well as the mechanism by which the microparticle containing an antigen is incorporated in its entirety into an immunocyte and releases the antigen in the cell are important, and that the function of drug release from the particle and the performance as an adjuvant are not necessarily correlated with each other. Therefore, it is difficult to infer the adjuvant function based on the sustained-release performance of the particle, and an effective adjuvant having a much better performance than aluminum adjuvants has not been realized so far by conventional technologies using microparticles in spite of the demand for its development.
There is, therefore, a need to provide an immunogenic composition which shows a high immune-activating capacity even with a small antigen amount and/or a small number of doses.